T-2307
目录号 : GC63675
T-2307 是一种芳基脒，在体外和体内具有抗真菌活性。T-2307 具有广谱抗菌活性，包括念珠菌属 (Candida， MIC 为 0.00025 至 0.0078 μg/mL)、新型隐球菌属 (Cryptococcus neoformans，MIC 为 0.0039-0.0625 μg/mL) 和曲霉属 (Aspergillus；MIC 为 0.0156-4 μg/mL)。
Cas No.:873546-31-7
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
T-2307, an arylamidine, has antifungal activities in vitro and in vivo. T-2307 exhibits broad-spectrum activity against clinically significant pathogens, including Candida species (MIC range, 0.00025 to 0.0078 μg/ml), Cryptococcus neoformans (MIC range, 0.0039 to 0.0625 μg/ml), and Aspergillus species (MIC range, 0.0156 to 4 μg/mL) [1].
T-2307 exhibits potent activity against fluconazole-resistant and fluconazole-susceptible-dose-dependent Candida albicans strains as well as against azole-susceptible strains[1]. T-2307 shows efficacy in a murine model of candida glabrata infection despite in vitro trailing growth phenomena[2].
In mouse models of disseminated candidiasis, cryptococcosis, and aspergillosis, the ED50 of T-2307 were 0.00755, 0.117, and 0.391 mg/kg, respectively[1].
[1]. Junichi Mitsuyama, et al. In vitro and in vivo antifungal activities of T-2307, a novel arylamidine. Antimicrob Agents Chemother. 2008 Apr;52(4):1318-24.
[2]. Eio Yamada, et al. T-2307 shows efficacy in a murine model of Candida glabrata infection despite in vitro trailing growth phenomena. Antimicrob Agents Chemother. 2010 Sep;54(9):3630-4.
| Cas No. | 873546-31-7 | SDF | |
| 分子式 | C25H35N5O2 | 分子量 | 437.58 |
| 溶解度 | DMSO : 50 mg/mL (114.26 mM; ultrasonic and adjust pH to 3 with HCl) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2853 mL | 11.4265 mL | 22.853 mL |
| 5 mM | 0.4571 mL | 2.2853 mL | 4.5706 mL |
| 10 mM | 0.2285 mL | 1.1426 mL | 2.2853 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Review of T-2307, an Investigational Agent That Causes Collapse of Fungal Mitochondrial Membrane Potential
J Fungi (Basel) 2021 Feb 11;7(2):130.PMID:33670132DOI:10.3390/jof7020130.
Invasive infections caused by Candida that are resistant to clinically available antifungals are of increasing concern. Increasing rates of fluconazole resistance in non-albicans Candida species have been documented in multiple countries on several continents. This situation has been further exacerbated over the last several years by Candida auris, as isolates of this emerging pathogen that are often resistant to multiple antifungals. T-2307 is an aromatic diamidine currently in development for the treatment of invasive fungal infections. This agent has been shown to selectively cause the collapse of the mitochondrial membrane potential in yeasts when compared to mammalian cells. In vitro activity has been demonstrated against Candida species, including C. albicans, C. glabrata, and C. auris strains, which are resistant to azole and echinocandin antifungals. Activity has also been reported against Cryptococcus species, and this has translated into in vivo efficacy in experimental models of invasive candidiasis and cryptococcosis. However, little is known regarding the clinical efficacy and safety of this agent, as published data from studies involving humans are not currently available.
The Arylamidine T-2307 as a Novel Treatment for the Prevention and Eradication of Candida tropicalis Biofilms
Int J Mol Sci 2022 Dec 16;23(24):16042.PMID:36555687DOI:10.3390/ijms232416042.
Candida tropicalis is an emerging pathogen with a high mortality rate due to its virulence factors, including biofilm formation, that has important repercussions on the public health system. The ability of C. tropicalis to form biofilms, which are potentially more resistant to antifungal drugs and the consequent increasing antimicrobial resistance, highlights an urgent need for the development of novel antifungal. The present study analyzed the antibiofilm capacity of the arylamidine T-2307 on two strains of Candida tropicalis. Antimicrobial activity and time-killing assays were performed to evaluate the anticandidal effects of T-2307, the antibiofilm ability on biomass inhibition and eradication was evaluated by the crystal violet (CV) method. Furthermore, in Galleria mellonella infected larvae an increased survival after pre-and post- treatment with T-2307 was observed. The MTT test was used to determine the viability of immortalized human prostate epithelial cells (PNT1A) after exposure to different concentrations of T-2307. Levels of interleukin IL-4, IL-8, IL-10 were quantified after Candida infection of PNT1A cells and treatment. Active doses of T-2307 did not affect the viability of PNT1A cells, and drug concentrations of 0.005 or 0.01 µg mL-1 inhibited the secretion of inflammatory cytokines. Taken together, these results provide new information on T-2307, indicating this drug as a new and promising alternative therapeutic option for the treatment of Candida infections.
T-2307, a novel arylamidine, is transported into Candida albicans by a high-affinity spermine and spermidine carrier regulated by Agp2
J Antimicrob Chemother 2016 Jul;71(7):1845-55.PMID:27090633DOI:10.1093/jac/dkw095.
Objectives: T-2307, a novel arylamidine, exhibits potent broad-spectrum activities against pathogenic fungi, particularly Candida albicans. We previously reported that T-2307 uptake was mainly mediated by a saturable high-affinity carrier at the MIC for C. albicans. Since we hypothesized that the potent anticandidal activity arose from accumulation via the high-affinity carrier, we characterized the specificity and kinetic features of the carrier. Methods: The MICs of T-2307 for C. albicans strains were evaluated in the presence and absence of potential competitive substrates. The cells were exposed to [(14)C]T-2307, [(14)C]spermine or [(14)C]spermidine in the presence of unlabelled T-2307, pentamidine, propamidine, or competitive substrates if necessary, and the radioactivity in the cells was measured. C. albicans gene deletion was performed using a one-step PCR-based technique. Results: Coapplication with exogenous spermine or spermidine decreased the antifungal activity and uptake of T-2307 in C. albicans strains. T-2307 competitively inhibited spermine and spermidine uptake with inhibition constants similar to its Km for the high-affinity carrier. The comparison of MICs and kinetic values between T-2307 and other diamidine compounds suggested that the different antifungal properties could be partially attributable to the variations in their affinity with the carrier. Studies of gene deletion mutants revealed that T-2307 was transported into C. albicans by a high-affinity spermine and spermidine carrier regulated by Agp2. Conclusions: Uptake of T-2307 via the high-affinity spermine and spermidine carrier regulated by Agp2 could contribute to its potent antifungal activity. Further investigation is required to identify the high-affinity carrier for potential targeting with novel therapies.
The Novel Arylamidine T-2307 Selectively Disrupts Yeast Mitochondrial Function by Inhibiting Respiratory Chain Complexes
Antimicrob Agents Chemother 2019 Jul 25;63(8):e00374-19.PMID:31182539DOI:10.1128/AAC.00374-19.
The novel arylamidine T-2307 exhibits broad-spectrum in vitro and in vivo antifungal activities against clinically significant pathogens. Previous studies have shown that T-2307 accumulates in yeast cells via a specific polyamine transporter and disrupts yeast mitochondrial membrane potential. Further, it has little effect on rat liver mitochondrial function. The mechanism by which T-2307 disrupts yeast mitochondrial function is poorly understood, and its elucidation may provide important information for developing novel antifungal agents. This study aimed to determine how T-2307 promotes yeast mitochondrial dysfunction and to investigate the selectivity of this mechanism between fungi and mammals. T-2307 inhibited the respiration of yeast whole cells and isolated yeast mitochondria in a dose-dependent manner. The similarity of the effects of T-2307 and respiratory chain inhibitors on mitochondrial respiration prompted us to investigate the effect of T-2307 on mitochondrial respiratory chain complexes. T-2307 particularly inhibited respiratory chain complexes III and IV not only in Saccharomyces cerevisiae but also in Candida albicans, indicating that T-2307 acts against pathogenic fungi in a manner similar to that of yeast. Conversely, T-2307 showed little effect on bovine respiratory chain complexes. Additionally, we demonstrated that the inhibition of respiratory chain complexes by T-2307 resulted in a decrease in the intracellular ATP levels in yeast cells. These results indicate that inhibition of respiratory chain complexes III and IV is a key factor for selective disruption of yeast mitochondrial function and antifungal activity.
T-2307 causes collapse of mitochondrial membrane potential in yeast
Antimicrob Agents Chemother 2012 Nov;56(11):5892-7.PMID:22948882DOI:10.1128/AAC.05954-11.
T-2307, an arylamidine compound, has been previously reported to have broad-spectrum in vitro and in vivo antifungal activities against clinically significant pathogens, including Candida species, Cryptococcus neoformans, and Aspergillus species, and is now undergoing clinical trials. Here we investigated the mechanism of action of T-2307 using yeast cells and mitochondria isolated from yeast and rat liver. Nonfermentative growth of Candida albicans and Saccharomyces cerevisiae in glycerol medium, in which yeasts relied on mitochondrial respiratory function, was inhibited at 0.001 to 0.002 μg/ml (0.002 to 0.004 μM) of T-2307. However, fermentative growth in dextrose medium was not inhibited by T-2307. Microscopic examination using Mitotracker fluorescent dye, a cell-permeant mitochondrion-specific probe, demonstrated that T-2307 impaired the mitochondrial function of C. albicans and S. cerevisiae at concentrations near the MIC in glycerol medium. T-2307 collapsed the mitochondrial membrane potential in mitochondria isolated from S. cerevisiae at 20 μM. On the other hand, in isolated rat liver mitochondria, T-2307 did not have any effect on the mitochondrial membrane potential at 10 mM. Moreover, T-2307 had little inhibitory and stimulatory effect on mitochondrial respiration in rat liver mitochondria. In conclusion, T-2307 selectively disrupted yeast mitochondrial function, and it was also demonstrated that the fungal mitochondrion is an attractive antifungal target.